The NIH Consensus Panel 2000 described osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. The long-term objective of the proposed study is to learn whether serum follicle stimulating hormone (FSH) could be used clinically as a biomarker to identify younger postmenopausal women with significant declines in the two measurable components of bone strength: areal bone mineral density (measured by dual-energy x-ray absorptiometry) and bone quality (assessed by peripheral quantitative computed tomography [pQCT]). Associations between FSH-related variables and low bone density have been reported in animal models and a cohort study of pre- and perimenopausal women;however, no study to date has tested for a possible relationship between FSH and bone quality. In a study of 16 postmenopausal women aged 50 to 64 years, we found a moderate and statistically significant unadjusted correlation between the multiplicative variable FSH-years and areal bone density in the distal radius. In the proposed project, we will also test for correlations between FSH-related variables and pQCT measures of bone quality in the distal forearm, accounting for hormonal influences on bone. Specific Aims: 1) In a cross-sectional study of 111 postmenopausal women aged 50 to 64 years recruited from primary care clinics, evaluate the relationship between serum FSH and: a) bone quality, b) bone mineral density, c) bone turnover;2) Test whether FSH is independently associated with bone quality and bone mineral density in the distal radius, adjusted for other hormonal factors. Our multidisciplinary research team has conducted a study of bone- related biomarkers in the NIH-funded General Clinical Research Center at the University of North Carolina since February 2005. We will extend this study to include new hormonal measures and specialized analysis of pQCT imaging of bone for the proposed project. Results will show whether future studies should test the diagnostic accuracy of FSH to identify high-risk younger postmenopausal women who could benefit from preventive interventions before the recommended age for routine osteoporosis screening. PROJECT NARRATIVE Osteoporosis is a condition of low bone strength that leads to high fracture-related morbidity and mortality in elderly women. This study will examine the potential for serum FSH to be used clinically as a biomarker of low bone strength in younger postmenopausal women.